The chimpanzee is the only nonhuman primate that can be reproducibly infected with HIV-1. Typically, infection with HIV-1 in the chimpanzee does not lead to disease. As such, these animals have mainly been used as a system for testing vaccines designed to prevent infection. The Yerkes Center houses 10 HIV-1-infected chimpanzees, most of which have been infected for over 10 years. It has become important to continue to analyze these animals for resistance to disease development and for evidence of progression, so that insights may be applied to treatments and therapies for humans. One animal, C499, developed clinical illness (diarrhea) in late 1995 which was associated with thrombocytopenia and a depressed CD4+ cell count. This animal continued to decline clinically, and was euthanatized in February 1996. Results from analysis of C499 showed that, in addition to thrombocytopenia, anemia, and CD4+ cell decline, the animal had a disseminated Cryptosporidium infection in the gastrointestinal tract. The Cryptosporidium infection is an AIDS-defining opportunistic infection. These analyses thus confirmed that C499 had AIDS. Analysis of the HIV-1 envelope gene derived from C499 showed that it was more closely related to HIV-1LAI than to other isolates, although the amino acid identity was only 84%. At the time that C499 developed illness, blood was transfused from this animal to an uninfected animal, C455, to further examine the pathogenesis of virus infection. C455 developed a rapid and sustained CD4+ cell decline. By 8 weeks following transfusion, the CD4+ cell level had reached 20/ul. This CD4+ cell depression has continued to date. Plasma viral loads in C455 were extremely high at 2 and 4 weeks post transfusion (up to 8 x 107 copies/ml), but have since leveled off at 105 copies/ml. More recently, C455 has developed a thrombocytopenia, apparently linked to HIV infection. Analysis of the virus present in C455 showed that it retained the ability to induce syncytium formation in chimpanzee PBMC, suggesting that this virus is responsible for the dramatic CD4+ cell decline. Other animals in this cohort appear to be progressing as evidenced by sustained CD4+ cell decline and lymph node pathology; two additional animals have also developed thrombocytopenia. Continuing analysis of these animals will provide important data concerning the pathogenesis of progression to AIDS, including the changes involved in the virus populations present in these animals.